I cover cardiology news for CardioExchange, a social media website for cardiologists published by the New England Journal of Medicine. I was the editor of TheHeart.Org from its inception in 1999 until December 2008. Following the purchase of TheHeart.Org by WebMD in 2005, I became the editorial director of WebMD professional news, encompassing TheHeart.Org and Medscape Medical News. Prior to joining TheHeart.Org, I was a freelance medical journalist and wrote for a wide variety of medical and computer publications. In 1994-1995 I was a Knight Science Journalism Fellow at MIT. I have a PhD in English from SUNY Buffalo, and I drove a taxicab in New York City before embarking on a career in medical journalism. You can follow me on Twitter at: @cardiobrief.

FDA Approves Lomitapide For Homozygous Familial Hypercholesterolemia

Aegerion Pharmaceuticals said today that the FDA had approved lomitapide (Juxtapid) to help further lower cholesterol in patients with homozygous familial hypercholesterolemia. The approval comes with a box warning about the risk of hepatotoxicity and a Risk Evaluation and Mitigation Strategy (REMS) Program which will require certification of health care providers and pharmacies before the drug can be prescribed and dispensed. The drug is expected to cost between $200,000-$300,000 per year.

The novel drug, which is a microsomal triglyceride transfer protein inhibitor is indicated, according to the label, “as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH)” The label notes that the safety and effectiveness of the drug has not been established in hypercholesterolemia patients who do not have homozygous FH and that the effect of the drug on cardiovascular morbidity and mortality has not been determined.

CAMBRIDGE, Mass., Dec. 24, 2012 (GLOBE NEWSWIRE) – Aegerion Pharmaceuticals, Inc. (Nasdaq:AEGR), a biopharmaceutical company dedicated to the development and commercialization of novel, life-altering therapies for patients with debilitating, often fatal, rare diseases, today announced that the U.S. Food & Drug Administration (FDA) has approved JUXTAPID™ (lomitapide) capsules as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B) and non- high-density-lipoprotein cholesterol (non-HDL) in patients with homozygous familial hypercholesterolemia (HoFH).

“We are excited that JUXTAPID will become a new treatment option for patients with HoFH,” said Marc Beer, Chief Executive Officer at Aegerion. “The approval of our first product also marks an important corporate milestone for Aegerion and reflects our commitment to help patients in need.”

HoFH is a serious, rare genetic disease that impairs the function of the receptor responsible for removing LDL-C (“bad” cholesterol) from the body. A loss of LDL receptor function results in extreme elevation of blood cholesterol levels. HoFH patients often develop premature and progressive atherosclerosis, a narrowing or blocking of the arteries.

“The FDA approval of JUXTAPID is a major step forward for HoFH patients and their families, who have long been waiting for new therapies,” said Katherine Wilemon, president and founder of The FH Foundation. “New treatments, combined with further understanding and awareness of this disease, can bring much needed hope to the HoFH community.”

JUXTAPID contains a Boxed Warning citing the risk of hepatic toxicity. See below for Important Safety Information about JUXTAPID, including the Boxed Warning, Contraindications and Warnings and Precautions. The safety and effectiveness of JUXTAPID have not been established in patients with hypercholesterolemia who do not have HoFH. The effect of JUXTAPID on cardiovascular morbidity and mortality has not been determined. The safety and effectiveness of JUXTAPID have not been established in pediatric patients.

The FDA based its approval of JUXTAPID on Aegerion’s pivotal Phase III study, which evaluated the safety and effectiveness of the medicine to reduce LDL-C levels in 29 adult patients with HoFH. The study was a multinational, single-arm, open-label, 78 week trial that was recently published in the November 2, 2012 online version of the Lancet. In this study, JUXTAPID was initiated at 5 mg daily and gradually escalated to doses of 10 mg, 20 mg, 40 mg, up to 60 mg, based on tolerability and acceptable liver enzymes levels.

When added to the existing lipid-lowering therapy of the HoFH patients in the study, JUXTAPID significantly reduced LDL-C from a baseline average of 336 mg/dL to 190 mg/dL (40% reduction) at Week 26 in the intent-to-treat population with last observation carried forward for the patients who discontinued prematurely. LDL-C was reduced by an average of 50 percent for the 23 patients who completed the study through Week 26. After Week 26, during the safety phase of the study, adjustments to concomitant lipid-lowering treatments were allowed. Average reductions in LDL-C were sustained during chronic therapy.

The most common adverse reactions in the Phase III trial were gastrointestinal, reported by 27 (93%) of 29 patients. Adverse reactions, which were reported by ≥8 patients (28%) in the HoFH clinical trial, included diarrhea, nausea, vomiting, dyspepsia and abdominal pain. Other common adverse reactions, reported by 5 to 7 (17-24%) patients, included weight loss, abdominal discomfort, abdominal distension, constipation, flatulence, increased ALT, chest pain, influenza, nasopharyngitis, and fatigue. Elevations in liver enzymes and hepatic (liver) fat were also observed. Ten of the 29 patients in the study had at least one elevation in liver enzymes greater than or equal to three times the upper limit of normal, including four patients who experienced liver enzymes greater than or equal to five times the upper limit of normal. Liver enzyme elevations were managed through dose reduction or temporary discontinuation of dose. There were no clinically meaningful elevations of total bilirubin, international normalized ratio (INR) or alkaline phosphatase, which are other markers of potential harmful effects on the liver. Hepatic fat increased from a baseline of 1 percent to a median absolute increase of 6 percent at 26 and 78 weeks.

Because of the risk of liver toxicity, JUXTAPID is available only through a restricted program called the JUXTAPID Risk Evaluation and Mitigation Strategy (REMS) Program. Aegerion will certify all health care providers who prescribe JUXTAPID and the pharmacies that will dispense the medicine. The goals of the REMS are:

To educate prescribers about:

the risk of hepatotoxicity associated with the use of JUXTAPID; and

the need to monitor patients during treatment with JUXTAPID as per product labeling.

To restrict access to therapy with JUXTAPID to patients with a clinical or laboratory diagnosis consistent with HoFH.

The safety and effectiveness of JUXTAPID have not been established in patients with hypercholesterolemia who do not have HoFH. The effect of JUXTAPID on cardiovascular morbidity and mortality has not been determined. The safety and effectiveness of JUXTAPID have not been established in pediatric patients.

To further understand JUXTAPID’s long-term safety and effectiveness, Aegerion has made a commitment to the FDA to conduct a post-approval, observational cohort study.

As part of the planned launch of JUXTAPID, the company has developed a comprehensive support services program for patients and their healthcare providers. For more information, call this toll-free number, 1-85JUXTAPID (1-855-898-2743).

Important Safety Information, including BOXED WARNING which states:

WARNING: RISK OF HEPATOTOXICITY

JUXTAPID can cause elevations in transaminases. In the JUXTAPID clinical trial, 10 (34%) of the 29 patients treated with JUXTAPID had at least one elevation in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or alkaline phosphatase.

JUXTAPID also increases hepatic fat, with or without concomitant increases in transaminases. The median absolute increase in hepatic fat was 6% after both 26 and 78 weeks of treatment, from 1% at baseline, measured by magnetic resonance spectroscopy. Hepatic steatosis associated with JUXTAPID treatment may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.

Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT and AST regularly as recommended. During treatment, adjust the dose of JUXTAPID if the ALT or AST are ≥3x ULN. Discontinue JUXTAPID for clinically significant liver toxicity.

Because of the risk of hepatotoxicity, JUXTAPID is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the JUXTAPID REMS Program.

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